1-1232666-G-T

Variant names:

• chr1-1232666-G-T
• rs777778007
• NM_080605.4:c.388G>T

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_080605.4(B3GALT6):​c.388G>T​(p.Glu130*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B3GALT6 NM_080605.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64
• Publications: 0 publications found

Genes affected

B3GALT6 (HGNC:17978): (beta-1,3-galactosyltransferase 6) The enzyme encoded by this intronless gene is a beta-1,3-galactosyltransferase found in the medial Golgi apparatus, where it catalyzes the transfer of galactose from UDP-galactose to substrates containing a terminal beta-linked galactose moiety. The encoded enzyme has a particular affinity for galactose-beta-1,4-xylose found in the linker region of glycosamines. This enzyme is required for glycosaminoglycan synthesis. [provided by RefSeq, Jun 2013]

B3GALT6 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, spondylodysplastic type, 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
• spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• spondyloepimetaphyseal dysplasia with joint laxity

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 25 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080605.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT6	NM_080605.4	MANE Select	c.388G>T	p.Glu130*	stop_gained	Exon 1 of 1	NP_542172.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GALT6	ENST00000379198.5	TSL:6 MANE Select	c.388G>T	p.Glu130*	stop_gained	Exon 1 of 1	ENSP00000368496.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1185148 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 576560

African (AFR) AF: 0.00 AC: 0 AN: 24352

American (AMR) AF: 0.00 AC: 0 AN: 18100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16814

East Asian (EAS) AF: 0.00 AC: 0 AN: 28830

South Asian (SAS) AF: 0.00 AC: 0 AN: 45512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4660

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 971378

Other (OTH) AF: 0.00 AC: 0 AN: 47034

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.6
Vest4		0.17
GERP RS		3.9
PromoterAI		-0.041	Neutral
Mutation Taster		=36/164	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs777778007; hg19: chr1-1168046;